3uic | pdb_00003uic

Crystal Structure of FabI, an Enoyl Reductase from F. tularensis, in complex with a Novel and Potent Inhibitor

spinqualitylabelsall models 3uic, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3uic is a 16 chain structure with sequence from "francisella_tularensis_subsp._nearctica"_olsufjev_1970 "francisella tularensis subsp. nearctica" olsufjev 1970. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 09T, NAD Gene: fabI, fabI Coordinates 801554-802336, FTT_0782 ("Francisella tularensis subsp. nearctica" Olsufjev 1970) Activity: [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Because of structural and mechanistic differences between eukaryotic and prokaryotic fatty acid synthesis enzymes, the bacterial pathway, FAS-II, is an attractive target for the design of antimicrobial agents. We have previously reported the identification of a novel series of benzimidazole compounds with particularly good antibacterial effect against Francisella tularensis, a Category A biowarfare pathogen. Herein we report the crystal structure of the F. tularensis FabI enzyme in complex with our most active benzimidazole compound bound with NADH. The structure reveals that the benzimidazole compounds bind to the substrate site in a unique conformation that is distinct from the binding motif of other known FabI inhibitors. Detailed inhibition kinetics have confirmed that the compounds possess a novel inhibitory mechanism that is unique among known FabI inhibitors. These studies could have a strong impact on future antimicrobial design efforts and may reveal new avenues for the design of FAS-II active antibacterial compounds. Structural and enzymatic analyses reveal the binding mode of a novel series of Francisella tularensis enoyl reductase (FabI) inhibitors.,Mehboob S, Hevener KE, Truong K, Boci T, Santarsiero BD, Johnson ME J Med Chem. 2012 Jun 28;55(12):5933-41. Epub 2012 Jun 8. PMID:22642319 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoyl-Acyl-Carrier Protein Reductase

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